Is TK1 p.Ala151Val (c.452C>T) pathogenic?

TK1 p.Ala151Val (c.452C>T) is classified Uncertain significance in TK1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.9848); Very rare (popmax 0.00669%, eas).

How common is TK1 p.Ala151Val (c.452C>T) in the general population?

TK1 p.Ala151Val (c.452C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about TK1 p.Ala151Val (c.452C>T)?

AlphaMissense predicts likely pathogenic (score 0.9848) — an in-silico prediction, not a clinical call.

TK1 p.Ala151Val

c.452C>T · VCV3326240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9848	likely pathogenic
REVEL	0.642	indeterminate
SaProt	LLR -13.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 12 kb · p 0.00027 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,848 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00118% 19/1,613,358 alleles · very rare exomes 19/1,461,254 · genomes 0/152,104 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,949
Admixed American	0.005%	19,989
European (non-Finnish)	0.0011%	90,760

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TK1
Protein: p.Ala151Val
Coding: c.452C>T
MANE Select: NM_003258
Type: single nucleotide variant
Location: chr17:78175111 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.72 · 4 PDB

Full TK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TK1 p.Ala198= Benign ★★ same type
TK1 p.Ala193Thr Uncertain significance ★ ⚠ same type
TK1 p.Arg186Trp Uncertain significance ★ ⚠ same type
TK1 p.Arg39Cys Uncertain significance ★ ⚠ same type
TK1 p.Arg41Cys Uncertain significance ★ ⚠ same type
TK1 p.Arg60His Uncertain significance ★ ⚠ same type
TK1 p.Arg70Trp Uncertain significance ★ ⚠ same type
TK1 p.Arg82Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tk1-p-ala151val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown